{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Txt":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE293nnn/GSE293934/suppl/filelist.txt"],"Raw":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE293nnn/GSE293934/suppl/GSE293934_RAW.tar"],"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE293nnn/GSE293934/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Homo sapiens"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE293934"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Inhibition of 5`- Cap Trimethylation Prevents Exosome Targeting of Telomerase RNA, Despite Promoting Increased 3`- end Oligoadenylation","description":"Mutations that impact maturation of human telomerase RNA (hTR) are common in telomere-biology disorders. Here, we describe sequential posttranscriptional modifications that coordinate hTR biogenesis and decay. Initially, TGS1-mediated 5`- cap trimethylation targets long genomically extended hTR precursors for degradation. Prevention of trimethylation results in accumulation of nucleolar 3`- end extended precursors, evading MTR4 recognition and degradation by the exosome, which in turn facilitates processing into mature hTR. In a second step, 3`- end oligoadenylation by PAPD5 promotes degradation of mature hTR, a process that remains dependent on 5`- cap modifications, as prevention of trimethylation inhibits decay of 3`- end oligoadenylated molecules. Combined inhibition of 5`- cap trimethylation and 3`- end oligoadenylation synergistically increases hTR in cells harboring pathogenic mutations in telomerase. These data reveal a precise interplay between 5`- and 3`- end posttranscriptional modifications that dictate hTR fate and highlight the potential of RNA therapeutics for treatment of telomere-biology disorders.","dates":{"publication":"2026/04/08"},"accession":"GSE293934","cross_references":{"GSM":["GSM8894780","GSM8894781","GSM8894782","GSM8894783","GSM8894784","GSM8894785","GSM8894786","GSM8894787","GSM8894788","GSM8894779"],"GPL":["15520"],"GSE":["293934"],"taxon":["Homo sapiens"],"PMID":["[41571462]"]}}